Botulinum toxin is a proteinous exotoxin secreted by Clostridium botulinum broadly distributed in soil and acts at the tips of the motor nerve endings at the neuromuscular junctions. When orally ingested into human body, the botulinum toxin gives rise to intoxication called botulism which is accompanied by paralytic symptoms. The botulism breaks out when the neurotoxin is absorbed from the alimentary tract and combines selectively with the presynaptic membranes at the peripheries of the neuromuscular junctions. The toxin thus interferes with the release of acetylcholine from the chlorinergic motor nerve endings and eventually with conduction of nerve impulses in the terminal branches of the motor nerves to cause neuromuscular relaxing and paralysis characteristic of the botulism. Death may occur from paralysis of respiratory muscles in the worst case.
As to the pathogenic mechanism of the botulinum toxin, it is established that the ganglioside GTlb, an acidic glycolipid present in the presynaptic membrane acts as a receptor for the toxin. While other types of gangliosides such as the gangliosides GQlb, GDlb and GDla also have the abilities of combining with botulinum toxin, these gangliosides are less potent than the ganglioside GTlb in combining with botulinum toxin and are, for this reason, considered less responsible for botulism.
The treatment of botulism is extremely difficult and, at the present time, there is practically no other method of treatment than to cease the symptoms once botulism is broken out. In view of the pathogenic mechanism of the botulinum toxin as above discussed, the first conceivable approach to the treatment of botulism may be to use the ganglioside GTbl as an antagonistic receptor for the botulinum toxin since the substance is capable of directly combining with the toxin. For this purpose, the ganglioside GTbl may be orally dosed into human body for direct attachment to the botulinum toxin to prevent the onset of the toxicity thereof. A problem is however encountered in that the source presently available of the ganglioside GTbl is none but the bovine brain, which is so expensive that the method of treating botulism with use of such a ganglioside has seldom been put into practice.
Under these circumstances, it is an object of the present invention to provide an economical botulinum toxin neutralizer which acts as if it were an antagonistic toxin receptor for the treatment of botulism and which will thus facilitate the prevention and treatment of botulism.